tbuckley/cabot-search huggingface dataset:
Abstract 13198: Cardiac TRPC6 N338S is a Gain-of-Function Mutation Associated With Doxorubicin-Induced Cardiomyopathy
Authors: Tong Lu, Nadine Norton, Hon-chi Lee
Journal: Circulation (2022)

Introduction: Doxorubicin (DOX) is widely used for chemotherapy, but cardiotoxicity and cardiomyopathy are major adverse effects. The canonical transient receptor potential 6 gene ( TRPC6) is a putative risk gene for cardiomyopathy. Recently, a TRPC6 N338S mutation was found in a patient with DOX-induced heart failure. However, the TRPC6 N338S mutant has not been characterized, and how it affects cardiac function is unknown. Hypothesis: We hypothesized that TRPC6 N338S is a gain-of-function mutation producing intracellular Ca 2+ overload in cardiomyocytes. Methods: Using patch clamp recording, molecular biological and molecular docking analyses, we assessed the function of TRPC6 N338S heterologously expressed in HL-1 cardiac cells. Results: TRPC6 N338S significantly increased the current densities of TRPC6 (defined as 1 μM BI-749327 sensitive components, a highly selective TRPC6 inhibitor) in HL-1 cells at baseline and after exposure to 50 μM 1-oleoyl 2-acetyl-sn-glycerol (OAG, an activator of TRPC6), compared to cells expressing TRPC6 WT. Moreover, a 24-h pretreatment with 0.5 μM DOX further potentiated the OAG effects on TRPC6 WT currents with a significantly greater response in the N338S currents. Ca 2+ imaging also showed enhanced intracellular Ca 2+ levels in cells expressing the N338S mutant with OAG and DOX treatment. Biological studies found that the cytoplasmic and surface expression of TRPC6 WT and N338S mutant were identical in HL-1 cells, but those of TRPC6 N338S were markedly upregulated after treatment with 0.5 μM DOX, compared to TRPC6 WT. Molecular docking and dynamics simulation analysis unraveled that OAG binds to a pocket constituted by the pore-helix, S5 and S6 domains of TRPC6 through polar interactions. OAG binds to the same site in TRPC6 N338S with shortened interfacial distances due to additional polar and hydrogen bonding between OAG and the N338S mutant. Conclusions: TRPC6 N338S mutation strengthens the interaction with OAG, stabilizes the OAG-TRPC6 N338S complex, and enhances the OAG effects. Treatment with DOX significantly increases the expression and function of TRPC6 N338S in HL-1 cells. Hence, the TRPC6 N338S is a gain-of-function mutation and may contribute to cardiotoxicity in patients with anthracycline treatment.
Abstract 13132: Uncontrolled Diabetes is Associated With Adverse Cardiovascular Disease Outcomes in Those With Stage B Heart Failure
Authors: Emmanuel P Lee, Chiadi E Ndumele, Sui Zhang, Kuni Matsushita, Hicham Skali, Amil M Shah, Elizabeth Selvin, Justin B Echouffo Tcheugui
Journal: Circulation (2022)

Background: Among persons with stage B heart failure (HF) (subclinical cardiac dysfunction), diabetes is associated with markedly increased risk of progression to clinical HF. Whether stage B HF indicates greater risk for other cardiovascular disease (CVD) outcomes in the presence of diabetes is unknown. Methods: We included ARIC Visit 5 (2011-13) participants without clinical HF who met criteria for stage A (HF risk factors) or stage B (subclinical cardiac dysfunction by echocardiogram or elevated cardiac biomarkers) HF. Across HF stages A and B, we calculated incidence rates and their differences and used Cox models to estimate hazard ratios for overall mortality, CVD mortality, coronary heart disease (CHD), and HF associated with controlled diabetes (HbA1c &lt;7%) and uncontrolled diabetes (HbA1c ≥ 7%), compared to no diabetes. Results: 4,774 participants (mean age 75.4, 58.3% women, 20.2% black) were followed for a median 7.3 years, with 867 deaths, 237 CVD deaths, 228 CHD events, and 470 HF events. There were significant additive interactions (increased absolute risk) associated with uncontrolled diabetes (vs. no diabetes) for total mortality, CVD death, CHD, and HF for stage B, but not stage A (Table). The incidence rate differences (per 1000 person-years) associated with uncontrolled diabetes (vs. no diabetes) were greater in stage B vs stage A for all outcomes (Table). In multivariable adjusted models, uncontrolled diabetes (vs. no diabetes) was associated with statistically significant hazard ratios (increased relative risk) for all CVD outcomes in stage B, but did not have significant associations with any CVD outcomes in stage A (Table). Conclusion: In stage B HF, diabetes is associated with global CVD risk. Intensive preventive efforts to avert various forms of CVD may be indicated for those with diabetes and subclinical cardiac dysfunction.
Abstract 13734: CardioNerds Narratives in Cardiology Tweetorials - Using Social Media to Elevate Discussions on Diversity and Inclusion
Authors: Gurleen Kaur, Karan Desai, Thomas M Das, Zarina Sharalaya, Saman Nematollahi, Daniel Ambinder, Joanna Ghobrial, Nosheen Reza, Kathryn Berlacher, Amit Goyal
Journal: Circulation (2022)

Introduction: Professional diversity is essential to addressing disparities in care but remains an unmet goal. The CardioNerds (a digital education platform) and Pennsylvania American College of Cardiology Chapter Narratives in Cardiology (NIC) multimodality series features faculty and trainees from underrepresented groups to share their professional and personal journeys with the aim to promote diversity and inclusion (D&amp;I). We created tweetorials (linked tweets on Twitter) with each podcast episode and evaluated each tweetorial’s ability to enhance users’ comfort with conversations around diversity. Methods: Between June 2021-March 2022, 7 NIC tweetorials were released. We evaluated the scope of reach using impressions (tweet appears to users), engagements (user interacts with tweet), and training level of interacting users at one-month. We assessed change in Twitter users’ self-reported comfort in discussing D&amp;I via poll question (Q1) at the beginning and end of the tweetorial: “I feel comfortable openly discussing or asking others about factors that make them different from myself⋯”. Users were also polled on “After reading this #CardsNarratives Tweetorial, I have a greater appreciation for diversity in cardiology” (Q2). Results: The 7 tweetorials had a total of 98,951 impressions and 2,717 engagements, with medical students or residents comprising 29% of interacting users. For Q1, there was a significant rise in the proportion of responders who answered “Agree” from 54% to 75% (ꭓ 2 =19.01, p &lt;0.05). After reviewing a given tweetorial, 88% of respondents reported having a greater appreciation for diversity in cardiology (Q2). Conclusions: Evaluation of the NIC tweetorials demonstrates successful reach to a broad audience including pre-cardiology trainees. This early report shows that tweetorials can elevate D&amp;I discussions and have the potential ability to positively impact users’ self-reported comfort with these topics.
Abstract 12770: Immune Checkpoint Inhibitor Induced Myocarditis: An Interesting Case of Reversible Complete Heart Block
Authors: Sasha Sharifi, likhitesh jaikumar, Christopher Smith, Vivek Menon, Anjula Chib, Dakshin Gangadharamurthy, MANDAR JAGTAP DO, Paul Volansky
Journal: Circulation (2022)

BACKGROUND: Immune checkpoint inhibitors (ICI) have changed the treatment scope for malignancies. The mechanism of ICIs is targeting of immune checkpoints that can suppress a response to a stimulus which can effect any organ. Adverse effects are usually mild but myocarditis, although rare, is becoming more recognized as a life threatening entity. The increase in mortality seen with ICI-induced myocarditis is more frequent with combination therapy. Most cases of ICI-induced myocarditis are limited to direct myocardial injury but there is a lack of evidence regarding conduction disease. CASE DESCRIPTION: We present a 74-year-old man with known metastatic malignancy recently started on ICI with ipilimumab and nivolumab who presented with complaints of abdominal pain, SOB and chest pain. His ED workup was consistent with colitis and acute PE without RV strain. Troponins and BNP were elevated and his ECG showed 3rd degree AV block. A coronary angiogram was negative for obstructive CAD and a temporary trans-venous pacemaker was placed. Cardiac MR showed LGE with active inflammation of the mid-myocardium. The patient had complex presentation as a side effect of ICI leading to myocarditis, 3rd degree AV block, colitis and PE. He was started on high dose methylprednisolone 1gm daily. Within 24 hours there was improvement evidenced by intermittent return of intrinsic conduction. At 48 hours there was marked improvement with restoration of sinus rhythm without evidence of AV block and/or use of the temporary pacemaker. Discussion: Early recognition of disease processes is difficult when there is minimal data to support a cause and effect. Increasing clinical awareness regarding adverse effects of ICI is paramount in decreasing the risk for unnecessary therapies, in our case, placement of a permanent pacemaker. Although there have been case reports of ICI-induced myocarditis, there has not been expert consensus regarding management of conduction pathway abnormalities.
Abstract 13059: Associations of Tobacco, Nicotine, and Cannabis Use With Covid-19 and Other Respiratory Infections—Results From the American College Health Association-National College Health Assessment (ACHA-NCHA)
Authors: Hy Tran, Brian Hitsman, Joshua Y Yoo, Erica N Fox, Donald Lloyd-Jones, Thanh-Huyen T Vu
Journal: Circulation (2022)

Background: Tobacco use is the single most preventable cause of cardiovascular disease mortality and morbidity. However, evidence on associations of tobacco/nicotine and cannabis use and COVID-19 infection and severity among youth is limited. It is also unclear if associations between tobacco and cannabis use with COVID-19 are similar to other acute respiratory infections (ARIs). Methods: We used data from Fall-2020 and Spring-2021 ACHA-NCHA surveys. Multivariable multinomial and binary logistic regression models were used to estimate the odds of COVID-19 infection/severity and other ARIs by tobacco/nicotine product or cannabis use within last 3 months. Results: Of 69,868 students ages 18-24, 70% were female, 0.7% with COVID-19 confirmed-severe, 5% confirmed-moderate, 8% confirmed-mild/asymptomatic, 23% with any ARIs, 18% using any tobacco/nicotine products, and 16% using cannabis. With multiple adjustments, users of only e-cigarettes, only other tobacco products, or dual/poly products (vs. non-users) were nearly 2 times more likely to have COVID-19 (vs. confirmed-negative). A similar pattern of associations was observed for tobacco/nicotine product use and ARIs. Cannabis use had no association with COVID-19 infection, but cannabis users had 8% higher odds of ARIs than non-users. Of 9,380 COVID-19 confirmed students, no association of tobacco/nicotine product use with COVID-19 severity was observed, but cannabis users had 17% higher odds of severe/moderate (vs. mild/asymptomatic) symptoms than non-users. Conclusion: Aong US college students, e-cigarette or dual/poly-product users are more likely to have COVID-19 and other acute respiratory infections. Cannabis users were more likely to have more severe COVID-19 symptoms than non-users; they were also more likely to have other acute respiratory infections.
Abstract 13539: The Effect of Emergency versus Delayed Coronary Angiography After Out-of-Hospital Cardiac Arrest Without ST-segment Elevation: A Meta-Analysis of Randomized Clinical Trials
Authors: Mohamed T Abuelazm, Ahmed K. Awad, Sarya Swed, Basel Abdelazeem, Nischit Baral, pramod savarapu, Annabelle S Santos Volgman
Journal: Circulation (2022)

Introduction. The prognosis of patients with out-of-hospital cardiac arrest (OHCA) is poor, with high mortality rates and poor neurological outcomes. Early coronary angiography (CAG) is recommended in patients with ST-segment elevation myocardial infarction (STEMI) associated with cardiac arrest; however, performing early or delayed CAG in patients with OHCA without STEMI is unclear. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to investigate the efficacy of early versus delayed CAG in patients with OHCA without STEMI. Methods. We searched Web of Science, SCOPUS, EMBASE, PubMed (MEDLINE), and CENTRAL from inception till June 2022. We included only RCTs that compared early versus delayed CAG in patients with OHCA. The main outcomes were percutaneous coronary intervention (PCI) rate, 30-day all-cause mortality, and neurological recovery (cerebral performance category (CPC) &lt; 3). We used the fixed-effect model to pool the risk ratio (RR) with a 95% confidence interval (CI). Results. We included seven RCTs with a total of 2104 patients. The overall risk ratio showed no difference between early and delayed CAG regarding PCI rate (RR: 1.06 with 95% [0.92, 1.23] p= 0.43), 30 days mortality (RR: 1.08 with 95% CI [0.97, 1.20] p= 0.15, and neurological recovery (RR: 1.04 with 95% CI [0.95, 1.13] p= 0.4). Conclusion. Among patients who experience an OHCA without STEMI, a strategy of performing early CAG provided no benefits in respect to the rate of PCI, 30 days mortality, and neurological recovery compared to delayed CAG.
Abstract 12981: Non-Conventional Causes of ST-Elevation Myocardial Infarction: Essential Thrombocytosis
Authors: Cole G Block, Kenneth Brownell, Menhel Kinno
Journal: Circulation (2022)

Case: A 61-year-old female with no significant past medical history, except hospitalization for COVID-19 pneumonia complicated by myocarditis ten months prior, presented to the emergency department with worsening chest pain over the last two weeks. The admission electrocardiogram (ECG) was without ischemic changes. The initial impression was that the patient's symptoms were attributed to her prior myocarditis. However, a repeat ECG obtained six hours later, due to worsening chest pain, demonstrated ST-segment elevations in leads V2, I and AVL. Emergent coronary angiography was performed, showing a 90% occlusion of the proximal LAD, which was managed with a drug-eluting stent. Admission platelet count was significantly elevated at 1,049,000mm 3 , which resulted in a hematology consultation. Her further work up included a positive JAK2-V617F mutation and negative BCR-ABL1 translocation, which confirmed the diagnosis of essential thrombocythemia. During the prior hospitalization for her COVID pneumonia, she underwent invasive coronary angiogram for suspected myocardial infarction in the setting of elevated troponin, which showed a mild, non-obstructive lesion in the proximal LAD. She underwent a cardiac MRI that demonstrated both sub-epicardial and mid-wall late gadolinium enhancement consistent with myocarditis. Discussion: Essential thrombocythemia is a clonal myeloproliferative disease caused by a pathological expansion of megakaryocytes, which results in excess platelet production. Essential thrombocythemia leads to a hematologic hyper-viscosity and subsequent increased risk of vasomotor, thrombotic and hemorrhagic manifestations. Myocardial infarction as the primary clinical presentation of essential thrombocythemia is rare but an important risk factor that should be considered in patients presenting with acute coronary syndromes and elevated platelet counts, both with and without traditional cardiovascular risk factors.
Abstract 12990: A Strange Case of Pericarditis: Pericarditis With Pneumopericardium Caused by a Misplaced G Tube
Authors: Ashwin Mahesh, Eduardo M Padrao, Kangwook Huh, Brian P Bustos, Joyce Meng
Journal: Circulation (2022)

Introduction: Most cases of pericarditis are idiopathic, consideration of other differentials remains essential. We present a 53 year-old-male who presented with pericarditis with pneumopericardium caused by a misplaced gastrostomy tube (G-tube). Case Description: A 53 year-old-male with autosomal dominant polycystic kidney disease on hemodialysis, encapsulating peritoneal sclerosis with percutaneous G-Tube for decompression, presented to the hospital with an acute sharp left sided chest pain. Vitals were unremarkable except for tachycardia. Physical exam revealed abdominal distension with tenderness elicited in the right upper quadrant and epigastric regions, with a G-tube in place with no erythema or tenderness along skin. A rub or pulsus paradoxus was not appreciated. EKG showed sinus tachycardia with diffuse ST elevations suggestive of acute pericarditis. Blood work including troponins were unremarkable except for BUN of 104 mg/dL. In suspicion of uremia, daily hemodialysis was initiated with prednisone. Patient did not respond to therapy despite improvement in uremia. CT imaging revealed a pneumopericardium [Tan arrow - Figure 1] which was in communication with the G-Tube, dislodged from its initial position [White arrow - Figure 1]. The G-Tube was later clamped and an echocardiogram revealed a small posterior pericardial effusion without tamponade. Patient later underwent surgical removal of the G-Tube followed by endoscopic suture closure of the fistula with symptom resolution. Conclusion: Although idiopathic pericarditis encompasses most of the cases, concerns should be raised for those patients that have atypical presentations, comorbidities and who do not respond to initial therapy.
Abstract 12970: Predictors of Stroke and Mortality in Children Who Undergo Ventricular Assist Device Placement: An Evaluation of Pre And Post-Operative Risk Factors Linked From the Advanced Cardiac Therapies Improving Outcomes Network (action) and Pediatric Cardiac Critical Care Consortium (pc4) Registries
Authors: Tanya Perry, David N Rosenthal, Angela Lorts, Farhan Zafar, Wenying Zhang, Christina J Vanderpluym, Aaron G DeWitt, Garrett Reichle, Mousumi Banerjee, Kurt Schumacher
Journal: Circulation (2022)

Introduction: Ventricular assist devices (VAD) have improved outcomes in children with advanced heart failure. However, despite improvements in adverse event rates, mortality and early post-VAD stroke remain important consequences. We sought to determine pre and post-operative factors that increase the risk of these outcomes utilizing data linked from the ACTION and PC4 registries. Methods: ACTION and PC4 registries are audited, comprehensive, encounter-based registries of patient course and outcomes for pediatric heart failure and pediatric cardiac critical care respectively. Data from patients who underwent initial VAD placement in each registry from 8/2014-7/2020 were linked using indirect patient identifiers. Patient demographics, heart disease, pre and post-operative ICU courses and outcomes were compiled. Appropriate descriptive and univariate statistics assessed association of patient factors with hospital mortality and stroke. Multivariable logistic regression sought independent associations with these outcomes. Results: 248 ACTION subjects were linked to a matching patient in PC4 with 98% match concordance. Median age was 7.7 years (1.5-15.5), weight 21.3kg (9.1-58) and 56% male. The cohort had 66% LVAD, 23% Single ventricle VAD and 10% BiVAD. Of the devices, 52 (21%) were Berlin EXCOR, 95 (38%) intracorporeal continuous flow, and 30 (12%) temporary continuous flow. The primary diagnosis was congenital heart disease in 35% of patients. Overall, 32 patients (13%) had a stroke and 45 patients (18%) died prior to discharge. Multivariable analysis found risk factors for mortality included only congenital heart disease (OR=3.78 [95%CI: 1.16-12.29], p=0.027), INTERMACS profile 1 (OR=6.51 [95%CI: 1.08-39.26], p=0.041), post-operative hepatic dysfunction (OR=37.35 [95%CI: 4.39-317.76], p&lt;0.01) and stroke (OR=5.33 [95%CI: 1.4-20.31], p=0.014). For stroke, no significant independent predictors were identified. Conclusion: Critical care therapies are not independently associated with post-VAD hospital death or stroke. Post-operative liver injury and stroke were associated with mortality.
Abstract 13823: Impact of Obesity on Inpatient Mortality and Adverse Cardiovascular Events in Patients With Cannabis Use Disorder: A Population-Based Analysis in the United States
Authors: Rupak Desai, Avilash Mondal, Sahana Devakumar, Sirisha K Gara, OLUFEMI ODUGBEMI, Sahas Reddy Jitta, lakshmi Spurthi Kodali, Naga Amrutha Sai Yalla, Fnu Juveria, Aobo Li, Zarna Bambhroliya, Ankit Vyas
Journal: Circulation (2022)

Background: Cannabis use disorder (CUD) is growing more prevalent, particularly among the young, and has the potential to increase cardiac/ cerebrovascular disease risk. We sought to determine how obesity affects cardiovascular outcomes in young cannabis users. Methods: Using 2019's National Inpatient Sample and relevant ICD-10 codes, we identified and compared young (18-44 years) obese vs. non-obese patients hospitalized with CUD. The risks of all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE- all-cause mortality, AMI, cardiac arrest, and stroke) and sex/racial disparities were assessed in young CUD admissions with and without obesity after adjusting for confounders Results: Overall prevalence of obesity among the young CUD cohort (n:539125, Mean age 30 years) was 10.3 % (55725/ 539125). The obese cohort was relatively older (mean age 32 vs 30 years) and often had females (58.6 vs 42.2%), blacks (33.6 vs. 23.1%), patients from the lowest income quartile (0-25th) (43.2 vs 39.7%), western hospitals (23 vs 20.1%) with lower non-elective admissions (85.3 vs 88.2%). Hypertension, diabetes, hyperlipidemia, PVD, prior MI, TIA/Stroke were more frequently seen in the CUD-Obese cohort. The young obese cohort with CUD had significantly higher adjusted odds of MACCE (aOR1.41, 95%CI 1.25-1.60, p&lt;0.001) even after controlling other confounders. Males (aOR 1.63, 95%CI 1.39-1.90, p&lt;0.001) but not females, whites (aOR 1.56, 95%CI 1.29-1.89, p&lt;0.001) and blacks (aOR 1.30, 95%CI 1.06-1.58, p=0.011) with obesity had a higher risk of MACCE vs. the non-obese cohort. However, all-cause mortality was not found to be significantly higher in the young obese cohort with CUD (aOR 1.14 95%CI 0.80-1.63, p=0.473) [Table 1] . Conclusions: Obese cannabis users are 41% more likely to have a MACCE event during hospitalizations. Prospective studies are needed to examine cardiovascular consequences in cannabis users with established CVD risk factors.